A number of viruses exhibit bidirectional transport along microtubules following cell entry. Cytoplasmic dynein has been implicated in virus transport toward the nucleus, but the role of kinesins is poorly understood. They might either aid in virus infection, or serve in host defense. Adenovirus provides a simple model for addressing these questions and is the focus of this proposal. Prior studies from this lab worked out the mechanism for dynein recruitment to the adenovirus capsid, and identified roles for protein kinase A (PKA) in virus transport as well as in host cell defense. The Aims of the proposed studies are 1) to identify kinesins involved in plus end-directed adenovirus transport during the early stages of infection; 2) to determine the role of kinesins in host-adenovirus interactions; and 3) to test the effect of microtubule stabilization and posttranslational modifications on live adenovirus transport. The latter Aim will make use of high-resolution live adenovirus particle tracking analysis, and is designed to take advantage of and complement the Aims of other projects described in this Program Project application. The proposed investigation of adenovirus alone has important implications for understanding the cellular mechanisms involved in virus infection, identifying novel mechanisms for host cell defense, and improving the design of gene targeting vectors.